Human calcium channel α-1C/α-1D, α-2, β-1, and γsubunits and cells expressing the DNA

Abstract

Isolated DNA encoding each of human calcium channel alpha 1-, alpha 2-, beta - and gamma -subunits, including subunits that arise as splice variants of primary transcripts, is provided. Cells and vectors containing the DNA and methods for identifying compounds that modulate the activity of human calcium channels are also provided.

What is claimed is: 
     
       1. An isolated DNA molecule, comprising a sequence of nucleotides that encodes an α 1  -subunit of a human calcium channel selected from the group consisting of: an α 1C  subunit comprising the sequence of amino acids set forth in SEQ ID NO. 45;   an α 1D  subunit comprising the sequence of amino acids of the α 1  -subunit set forth in SEQ ID NO. 49; or comprising the sequence of amino acids of the α 1  -subunit set forth in SEQ ID NO. 151; and   a human calcium channel α 1  -subunit that is encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid human calcium channel α 1  -subunits, wherein: the α 1  -subunit is an α 1C  - or α 1D  -subunit; such that any probe that contains at least 14 contiguous bases from the coding portion of the α 1  -encoding DNA is capable of hybridizing under conditions of high stringency to the DNA that if fully complementary to the mRNA transcript.   
     
     
       2. The DNA molecule of claim 1, wherein the α 1  -subunit is a human neural calcium α 1  subunit. 
     
     
       3. The DNA molecule of claim 1, wherein the α 1  subunit is an α 1D  -subunit. 
     
     
       4. The DNA molecule of claim 1, wherein the α 1  subunit is an α 1C  -subunit. 
     
     
       5. A cultured eukaryotic cell, comprising heterologous DNA that encodes a human calcium channel α 1  -subunit and has the nucleotide sequence of the DNA molecule of claim 1 and heterologous DNA that encodes a human calcium channel α 2b  -subunit, wherein: the α 2b  subunit is a human calcium channel α 2b  -subunit comprising the amino acid sequence set forth in SEQ ID NO: 52 or a human calcium channel α 2b  subunit encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to the mRNA transcript native to a human cell that encodes the aforesaid human calcium channel α 2b  subunit such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the α 2b  -subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript; and   the cell is a mammalian cell or yeast cell.   
     
     
       6. The DNA molecule of claim 1, comprising the sequence of nucleotides set forth in SEQ ID No. 1, 3 or 23. 
     
     
       7. An isolated DNA molecule of claim 1 that encodes an α 1  -subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO. 3. 
     
     
       8. An isolated DNA molecule of claim 1 that encodes an α 1  -subunit of a human calcium channel, comprising sequence of nucleotides set forth in SEQ ID NO. 6. 
     
     
       9. An isolated DNA molecule of claim 1 that encodes an α 1  -subunit of a human calcium channel, comprising the sequence set forth in SEQ ID NO. 1. 
     
     
       10. An isolated DNA molecule of claim 1 that encodes an α 1  -subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO. 23. 
     
     
       11. An isolated and purified mRNA molecule degenerate with the DNA molecule of claim 1. 
     
     
       12. A cultured eukaryotic cell, comprising heterologous DNA having the sequence of the DNA molecule of claim 1, wherein the cell is a mammalian cell or a yeast cell. 
     
     
       13. The eukaryotic cell of claim 12, further comprising additional DNA encoding at least one subunit selected from the group consisting of a human calcium channel β-subunit, a human calcium channel α 2  -subunit, and a human calcium channel γ-subunit, wherein: the α 2  -subunit is selected from the group consisting of: an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 53,   an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 54,   an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 55,   an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 56, and   an α 2  -subunit comprising the amino acid sequence of an α 2a , α 2c , α 2d , or α 2e  subunit polypeptide, wherein the additional DNA encoding the α2-subunit is capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes the amino acid sequence set forth in SEQ ID NO: 53, 54, 55, or 56, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA encoding the α2-subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript that encodes an α 2  -subunit;     the β-subunit is selected from the group consisting of: a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 40,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 41,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 42,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 43,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 44, and   a human calcium channel β-subunit encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid β subunits, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the β-subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript that encodes a β-subunit;     the γ-subunit is selected from the group consisting of: a γ-subunit native to a human cell which comprises the sequence of amino acids set forth in SEQ ID NO: 57, and   a human calcium channel γ-subunit encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes the aforesaid γ-subunit, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the γ-subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript that encodes a γ-subunit.     
     
     
       14. The eukaryotic cell of claim 13, wherein the additional DNA comprises DNA encoding an α 2  -subunit of a human calcium channel selected from an α 2a , α 2c , α 2d  and α 2e  subunit. 
     
     
       15. The eukaryotic cell of claim 14, wherein the calcium channel is a human skeletal muscle calcium channel or human aortic calcium channel. 
     
     
       16. The eukaryotic cell of claim 13, wherein the additional DNA comprises DNA encoding a β-subunit of a human calcium channel. 
     
     
       17. The eukaryotic cell of claim 13, wherein the additional DNA comprises DNA encoding a γ-subunit of a human calcium channel. 
     
     
       18. The eukaryotic cell of claim 13, that has a functional heterologous voltage dependent calcium channel that contains at least one subunit encoded by the heterologous DNA, wherein the at least one subunit is an α 1  -subunit of a human calcium channel. 
     
     
       19. The eukaryotic cell of claim 18, wherein the functional heterologous voltage dependent calcium channel contains at least two subunits encoded by the heterologous DNA and the subunits encoded by the heterologous DNA, in addition to the α 1  -subunit, are a β-subunit or an α 2  -subunit. 
     
     
       20. The eukaryotic cell of claim 19, wherein the calcium channel contains at least three subunits that are encoded by the heterologous DNA. 
     
     
       21. The eukaryotic cell of claim 20, wherein the calcium channel contains four subunits encoded by the heterologous DNA. 
     
     
       22. The eukaryotic ell of claim 12 that has a functional heterologous voltage dependent calcium channel that contains a subunit encoded by the heterologous DNA, wherein the only heterologous ion channels that are expressed by the cell are calcium channels. 
     
     
       23. The eukaryotic cell of claim 22 selected from the group consisting of an HEK 293 cell, a Chinese hamster ovary cell, an African green monkey cell, and a mouse L cell. 
     
     
       24. The eukaryotic cell of claim 12 selected from the group consisting of HEK 293 cell, a Chinese hamster ovary cell, an African green monkey cell, and a mouse L cell. 
     
     
       25. An isolated eukaryotic cell with a functional, heterologous calcium channel, produced by a process comprising introducing into the cell at least one RNA transcript selected from the group consisting of a first RNA which is translatable in said cell into an α 1  -subunit of a human calcium channel, a second RNA which is translatable in said cell into a β-subunit of a human calcium channel, a third RNA which is translatable in said cell into an α 2  -subunit of a human calcium channel, and a fourth RNA which is translatable in said cell into a γ-subunit of a human calcium channel, wherein the cell is a mammalian cell, yeast cell, or amphibian oocyte, and wherein: the α 1  -subunit is selected from the group consisting of: an α 1C  -subunit comprising the sequence of amino acids set forth in SEQ ID NO: 45,   an α 1D  -subunit comprising the sequence of amino acids set forth in SEQ ID NO: 49 or SEQ ID NO: 51,   an α 1D  -subunit having the sequence of an α 1D  -subunit native to a human cell that comprises the sequence of amino acids set forth in SEQ ID NO: 50, and   a human calcium channel α 1  -subunit, wherein the α 1  -subunit is an α 1C  - or α 1D  -subunit encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid human calcium channel α 1  -subunits, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the α 1  -subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript that encodes an α 1  -subunit;     the α 2  -subunit is selected from the group consisting of: an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 53,   an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 54,   an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 55,   an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 56, and   an α 2  -subunit comprising the amino acid sequence of an α 2a , α 2c , α 2d , or α 2e  subunit polypeptide, wherein DNA encoding the α2-subunit is capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes the amino acid sequence set forth in SEQ ID NO: 53, 54, 55, or 56, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the α2-subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript that encodes an α 2  -subunit;     the β-subunit is selected from the group consisting of: a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 40,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 41,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 42,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 43,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 44, and   a human calcium channel β-subunit encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid β subunits, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the β-subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript that encodes a β-subunit;     the γ-subunit is selected from the group consisting of: a γ-subunit native to a human cell which comprises the sequence of amino acids set forth in SEQ ID NO: 57, and   a human calcium channel γ-subunit encoded by DNA capale of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that comprises the sequence of nucleotides set forth in SEQ ID NO: 14, wherein T residues are replaced by U, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the γ-subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript that encodes a γ-subunit; and     the only heterologous ion channels that are expressed by the cell are calcium channels.   
     
     
       26. The eukaryotic cell of claim 25 which is an amphibian oocyte. 
     
     
       27. An isolated eukaryotic cell with a functional heterologous calcium channel, produced by a process comprising introducing into the cell at least one RNA transcript that is translatable in the cell into an α 2  -subunit of a human calcium channel, and optionally introducing into the cell one or more RNA transcripts selected from the group consisting of an RNA that is translatable in the cell into an α 1  -subunit of a human calcium channel, an RNA that is translatable in the cell into a β-subunit of a human calcium channel, and an RNA that is translatable in the cell into a γ-subunit of a human calcium channel, wherein: the cell is a mammalian cell, yeast cell, or amphibian oocyte;   the only heterologous ion channels that are expressed by the cells are calcium channels; and   the α 2  subunit is a human calcium channel α 2b  -subunit comprising the amino acid sequence set forth in SEQ ID NO: 52 or a human calcium channel α 2b  subunit encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes the aforesaid human calcium channel α 2b  subunit such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the α 2b  -subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript.   
     
     
       28. The isolated eukaryotic cell of claim 27, wherein: the α 1  -subunit is selected from the group consisting of: an α 1C  -subunit comprising the sequence of amino acids set forth in ID NO: 45,   an α 1D  -subunit comprising the sequence of amino acids set forth in ID NO: 49 or SEQ ID NO: 51,   an α 1D  -subunit having the sequence of an α 1D  -subunit native to the human cell that comprises the sequence of amino acids set forth in SEQ ID NO: 50, and   a human calcium channel α 1  -subunit, wherein the α 1  -subunit is an α 1C  - or α 1D  -subunit encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid human calcium channel α 1  -subunits, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the α 1  -subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript that encodes an α 1  -subunit;     the β-subunit is selected from the group consisting of: a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 40,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 41,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 42,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 43,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 44, and   a human calcium channel β-subunit encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid human calcium channel β-subunits, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the β-subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript that encodes a β-subunit;     the γ-subunit is selected from the group consisting of: a γ-subunit native to a human cell which comprises the sequence of amino acids set forth in SEQ ID NO: 57, and   a human calcium channel γ-subunit encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that comprises the sequence of nucleotides set forth in SEQ ID NO: 14, wherein T residues are replaced by U, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the γ-subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript that encodes a γ-subunit; and     the only heterologous ion channels that are expressed by the cell are calcium channels.   
     
     
       29. An isolated DNA molecule, comprising a sequence of nucleotides that encodes an α 1  -subunit of a human calcium channel native to a human cell selected from the group consisting of: an α 1C  subunit comprising the sequence of nucleic acids set forth in SEQ ID NO: 45 or 46,   an α 1D  subunit comprising the sequence of amino acids set forth in SEQ ID NO: 49, 50, or 51, and   a human calcium channel α 1  -subunit that is encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid human calcium channel α 1  -subunits;   wherein the α 1  -subunit binds to at least one compound selected from the group consisting of a dihydropyridine, a phenylalkylamine, ω-CgTx, and a pyrazonoylguanidine.   
     
     
       30. An isolated DNA molecule, comprising a sequence of nucleotides that encodes an α 1  -subunit of a human calcium channel selected from the group consisting of: an α 1C  subunit comprising the sequence of nucleic acids set forth in SEQ ID NO: 45 or 46,   an α 1D  subunit comprising the sequence of amino acids set forth in SEQ ID NO: 49, 50, or 51, and   a human calcium channel α 1  -subunit that is encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid human calcium channel α 1  -subunits;   wherein the α 1  -subunit is a naturally occurring α 1C  or α 1D  -subunit.   
     
     
       31. An isolated DNA molecule, comprising a sequence of nucleotides encoding the sequence of amino acids set forth in SEQ ID NO: 45. 
     
     
       32. An isolated DNA molecule, comprising a sequence of nucleotides encoding a human calcium channel α 1C  subunit native to a human cell that comprises the sequence of amino acids set forth in SEQ ID NO: 46. 
     
     
       33. An isolated DNA probe, comprising the sequence of nucleotides set forth in SEQ ID NO: 2. 
     
     
       34. An isolated DNA probe, comprising a sequence of nucleotides that encodes the sequence of amino acids set forth in SEQ ID NO: 50. 
     
     
       35. An isolated DNA molecule, comprising a sequence of nucleotides encoding a human calcium channel α 1D  subunit native to a human cell that comprises the sequence of amino acids set forth in SEQ ID NO: 50. 
     
     
       36. An isolated DNA molecule, comprising a sequence of nucleotides encoding the sequence of amino acids set forth in SEQ ID NO: 49. 
     
     
       37. An isolated DNA molecule, comprising a sequence of nucleotides encoding the sequence of amino acids set forth in SEQ ID NO: 51. 
     
     
       38. An isolated DNA molecule, comprising a sequence of nucleotides that encodes an α 2  -subunit of a human calcium channel selected from the group consisting of: an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 53,   an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 54,   an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 55,   an α 2  -subunit comprising the sequence set forth in SEQ ID NO: 56, and   an α 2  -subunit comprising the amino acid sequence of an α 2a , α 2c , α 2d , or α 2e  subunit polypeptide, wherein the DNA molecule is capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes the amino acid sequence set forth in SEQ ID NO: 53, 54, 55, or 56, such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA molecule hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript.   
     
     
       39. A DNA molecule of claim 38, comprising a sequence of nucleotides that encodes an α 2d  -subunit. 
     
     
       40. An isolated DNA molecule of claim 38 that encodes an α 2  -subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO. 33. 
     
     
       41. An isolated DNA molecule of claim 38 that encodes an α 2  -subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO: 34. 
     
     
       42. An isolated DNA molecule of claim 38 that encodes an α 2  -subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO: 35. 
     
     
       43. An isolated DNA molecule of claim 38 that encodes an α 2  -subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO: 36. 
     
     
       44. An isolated and purified mRNA molecule degenerate with the DNA molecule of claim 38. 
     
     
       45. An isolated DNA molecule, comprising a sequence of nucleotides that encodes an α 2b  -subunit of a human calcium channel comprising the amino acid sequence set forth in SEQ ID NO: 52 or is a human calcium channel α 2b  subunit encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes the aforesaid human calcium channel α 2b  subunit such that any probe that contains at least 14 contiguous bases from the coding portion of the DNA that encodes the α 2b  -subunit hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript. 
     
     
       46. An isolated DNA molecule of claim 45 that encodes an α 2b  -subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO. 11. 
     
     
       47. An isolated DNA molecule, comprising a sequence of nucleotides that encodes: an α 2  -subunit of a human calcium channel comprising the amino acid sequence set forth in SEQ ID NO: 53, 54, 55, 56, or   a naturally occurring human calcium channel α 2  subunit, wherein the α 2  -subunit is an α 2a , α 2c , α 2d , or α 2e  subtype and is encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid human calcium channel α 2  -subunits.   
     
     
       48. An isolated DNA molecule, comprising the sequence of nucleotides set forth in SEQ ID No. 11. 
     
     
       49. An isolated DNA molecule, comprising the sequence of nucleotides set forth in SEQ ID Nos. 53, 54, 55 or 56. 
     
     
       50. An isolated DNA molecule, comprising a sequence of nucleotides that encodes a β-subunit of a human calcium channel selected from the group consisting of: a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 40,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 41,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 42,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 43,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 44, and   a human calcium channel β-subunit that is encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid β subunits, such that any probe containing 14 contiguous bases from the coding portion of the DNA molecule hybridizes under conditions of high stringency to the DNA that is fully complementary to the mRNA transcript.   
     
     
       51. The DNA molecule of claim 50, wherein the β subunit is a β 1-1 , β 1-2 , β 1-3 , β 1-4 , or β 1-5  subunit. 
     
     
       52. An isolated DNA molecule of claim 50 that encodes a β-subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO: 9. 
     
     
       53. An isolated DNA molecule of claim 50 that encodes a β-subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO: 10. 
     
     
       54. An isolated DNA molecule of claim 50 that encodes a β-subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO: 37. 
     
     
       55. An isolated DNA molecule of claim 50 that encodes a β-subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO: 38. 
     
     
       56. An isolated DNA molecule of claim 50 that encodes a β-subunit of a human calcium channel, comprising the sequence of nucleotides set forth in SEQ ID NO: 39. 
     
     
       57. An isolated and purified mRNA molecule degenerate with the DNA molecule of claim 50. 
     
     
       58. An isolated DNA molecule, comprising a sequence of nucleotides that encodes a naturally occurring β-subunit of a human calcium channel selected from the group consisting of: a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 40,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 41,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 42,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 43,   a β-subunit comprising the sequence of amino acids set forth in SEQ ID NO: 44, and   a human calcium channel β-subunit that is encoded by DNA capable of hybridizing under conditions of high stringency with DNA that is fully complementary to an mRNA transcript native to a human cell that encodes one of the aforesaid β subunits.   
     
     
       59. An isolated DNA molecule, comprising a sequence of nucleotides that encodes the sequence of amino acids set forth in SEQ ID NO: 40. 
     
     
       60. An isolated DNA molecule, comprising a sequence of nucleotides that encodes the sequence of amino acids set forth in SEQ ID NO: 41. 
     
     
       61. An isolated DNA molecule, comprising a sequence of nucleotides that encodes the sequence of amino acids set forth in SEQ ID NO. 42. 
     
     
       62. The DNA molecule of claim 58, comprising a sequence of nucleotides that encodes the amino acids set forth in SEQ ID NO. 43. 
     
     
       63. An isolated DNA molecule, comprising a sequence of nucleotides that encodes the sequence of amino acids set forth in SEQ ID NO: 44. 
     
     
       64. An isolated DNA molecule, comprising the sequence of nucleotides set forth in SEQ ID Nos: 9, 10, 37, 38 or 39.